crossing96/oncoscreening huggingface dataset:
The Clinical Application of Fluorescence in Situ Hybridization in Diagnosing Urothelial Carcinoma.	BACKGROUND: Chromosomal aberrations in exfoliated urothelial cells have been associated with the development of urothelial carcinoma. This study aimed to evaluate the efficacy of two kinds of fluorescence in situ hybridization (FISH) kit probes in diagnosing urothelial carcinoma (UC). METHODS: From February 2009 through September 2014, urine specimens from 89 consecutive patients with urothelial carcinoma and 11 controls with benign disease were collected and analyzed by means of GP FISH and cytology. Urine samples from 50 consecutive patients with urothelial carcinoma and 68 patients with non-urothelial carcinoma with hematuria were also collected and analyzed by UroVysion FISH and cytology. The sensitivity and specificity of two kinds of FISH and cytology in different stages and grades of urothelial carcinoma were statistically analyzed via SPSS 17.0 and compared. RESULTS: The overall sensitivity of GP FISH and cytology were 88.8% (79/89) and 55.1% (49/89), respectively (p < 0.001), and the overall specificity was 90.9% (10/11) and 100.0% (11/11), respectively (p > 0.05). The overall sensitivity of UroVysion FISH and cytology was 68.0% and 18.0%, respectively (p < 0.05), and the overall specificity was 91.2% and 98.5%, respectively (p > 0.05). The sensitivity of FISH and cytology in diagnosing UUT-UC were 88.9% (16/18) and 44.4%(8/18),respectively. The sensitivity of GP FISH and UroVysion FISH in diagnosing UUT-UC were 100% (10/10) and 75.0% (6/8) respectively. CONCLUSIONS: FISH is a non-invasive technique with higher sensitivity and similar specificity compared with urine exfoliated cell cytology in diagnosing urothelial carcinoma by detecting the aberrations of chromosome 3, 7, 17, and 9p21. FISH is significantly superior to cytology in diagnosing low stage and low grade urothelial carcinomas. FISH is a very valuable and promising technique in diagnosing urothelial carcinomas.	bladder
Can the Preoperative Neutrophil-to-Lymphocyte Ratio Significantly Predict the Conditional Survival Probability in Muscle-invasive Bladder Cancer Patients Undergoing Radical Cystectomy?	INTRODUCTION: The present study investigated the prognostic value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in bladder cancer patients undergoing radical cystectomy (RC), with a focus on the conditional survival (CS) estimates over time after surgery. MATERIALS AND METHODS: We analyzed 385 bladder cancer patients who underwent RC from 1999 to 2012. The patients were classified into 2 groups according to the preoperative NLR (< 2.5 vs. ≥ 2.5). The Kaplan-Meier survival analysis was used to calculate the conditional probabilities of cancer-specific survival and overall survival after surgery. Multivariate Cox regression models were used to identify the predictors of 5-year conditional cancer-specific survival and overall survival. RESULTS: Patients with an elevated preoperative NLR (≥ 2.5) had a greater proportion of advanced-stage tumors (≥ pT3), high-grade tumors, and lymphovascular invasion. Patients with an elevated preoperative NLR (≥ 2.5) had poor CS estimates compared with those with a lower NLR (< 2.5) at baseline and 1 year after RC. However, no significant differences in CS probabilities were observed from 2 years after RC onward. In a multivariate Cox regression analysis, the preoperative NLR was identified as a significant predictive factor for 5-year CS at baseline and postoperative 1-year estimation; however, its significance was lost after 2 years postoperatively. CONCLUSION: Our study results suggest that the dynamic aspect of the NLR should be considered when assessing the prognosis of bladder cancer patients treated with RC over time after the initial estimates, in particular, in patients who have already survived for additional years after surgery.	bladder
Discovery and validation of potential urinary biomarkers for bladder cancer diagnosis using a pseudotargeted GC-MS metabolomics method.	Bladder cancer (BC) is the second most prevalent malignancy in the urinary system and is associated with significant mortality; thus, there is an urgent need for novel noninvasive diagnostic biomarkers. A urinary pseudotargeted method based on gas chromatography-mass spectrometry was developed and validated for a BC metabolomics study. The method exhibited good repeatability, intraday and interday precision, linearity and metabolome coverage. A total of 76 differential metabolites were defined in the discovery sample set, 58 of which were verified using an independent validation urine set. The verified differential metabolites revealed that energy metabolism, anabolic metabolism and cell redox states were disordered in BC. Based on a binary logistic regression analysis, a four-biomarker panel was defined for the diagnosis of BC. The area under the receiving operator characteristic curve was 0.885 with 88.0% sensitivity and 85.7% specificity in the discovery set and 0.804 with 78.0% sensitivity and 70.3% specificity in the validation set. The combinatorial biomarker panel was also useful for the early diagnosis of BC. This approach can be used to discriminate non-muscle invasive and low-grade BCs from healthy controls with satisfactory sensitivity and specificity. The results show that the developed urinary metabolomics method can be employed to effectively screen noninvasive biomarkers.	bladder
Increased lncRNA ABHD11-AS1 represses the malignant phenotypes of bladder cancer.	Bladder cancer is one of the most common urothelial tumors worldwide. While there are some progresses on early bladder cancer detection, patients' mortalities have not been changed significantly. So it is important to get further understanding the mechanism involved in the development and progression of bladder cancer. Long non-coding RNAs play important regulatory roles in a variety of biological processes ranging from gene regulation, cellular differentiation to tumorigenesis. Previous literatures reported that lncRNA ABHD11 Antisense RNA 1 (ABHD11-AS1) (Organism: Homo sapiens) was highly expressed in gastric cancer. Inspired by these observations, we hypothesized that ABHD11-AS1 possibly plays an analogous role in human bladder cancer. We first found that ABHD11-AS1 was up-regulated in bladder cancer tissues and cell lines, and ABHD11-AS1 expression level was positively associated with clinicobiological features. Cell proliferation, cell migration and apoptosis were observed by silencing ABHD11-AS1 and overexpression ABHD11-AS1 caused contrary effects. Taken together, these data suggested that ABHD11-AS1 may be an oncogene and a therapeutic target in bladder cancer.	bladder
Targeted O-glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced-stage bladder tumours.	Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short-chain O-glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST), which are generally associated with poor prognosis. We have also explored the nature of T antigen sialylation, namely the sialyl-3-T(S3T) and sialyl-6-T(S6T) sialoforms, based on combinations of enzymatic treatments. We observed a predominance of sialoglycans over neutral glycoforms (Tn and T antigens) in bladder tumours. In particular, the STn antigen was associated with high-grade disease and muscle invasion, in accordance with our previous observations. The S3T and S6T antigens were detected for the first time in bladder tumours, but not in healthy urothelia, highlighting their cancer-specific nature. These glycans were also overexpressed in advanced lesions, especially in cases showing muscle invasion. Glycoproteomic analyses of advanced bladder tumours based on enzymatic treatments, Vicia villosa lectin-affinity chromatography enrichment and nanoLC-ESI-MS/MS analysis resulted in the identification of several key cancer-associated glycoproteins (MUC16, CD44, integrins) carrying altered glycosylation. Of particular interest were MUC16 STn(+) -glycoforms, characteristic of ovarian cancers, which were found in a subset of advanced-stage bladder tumours facing the worst prognosis. In summary, significant alterations in the O-glycome and O-glycoproteome of bladder tumours hold promise for the development of novel noninvasive diagnostic tools and targeted therapeutics. Furthermore, abnormal MUC16 glycoforms hold potential as surrogate biomarkers of poor prognosis and unique molecular signatures for designing highly specific targeted therapeutics.	bladder
Modifying Cationic Liposomes with Cholesteryl-PEG Prevents Their Aggregation in Human Urine and Enhances Cellular Uptake by Bladder Cancer Cells.	Intravesical drug delivery by cationic liposomes (Cat-LPs) represents a potent nanotechnology for enhancing therapeutic effects against bladder disorders. However, preventing the aggregation of Cat-LPs in urine poses a significant barrier. We report on an examination of the effect of modifying liposomes with polyethylene glycol (PEG) lipids to prevent Cat-LPs from aggregating in human urine. Although Cat-LPs underwent significant aggregation in human urine, introducing 5 mol% of PEG2k lipid or 2 mol% of PEG5k lipid completely inhibited the aggregation of the Cat-LPs. When 2 mol% of PEG2k lipids were introduced, the lipid structures of 1,2-distearoly-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-distearoyl-sn-glycerol (DSG) greatly prevented aggregation compared with cholesterol. By contrast, when Cat-LPs, after incubation in urine, were exposed to bladder cancer cells, only introducing cholesteryl-PEG into the Cat-LPs showed a significant enhancement in cellular uptake. These results offer the potential for incorporating cholesteryl-PEG into Cat-LPs for achieving both stability in urine and effective cellular uptake.	bladder
The marine triterpene glycoside frondoside A induces p53-independent apoptosis and inhibits autophagy in urothelial carcinoma cells.	BACKGROUND: Advanced urothelial carcinomas represent a considerable clinical challenge as they are difficult to treat. Platinum-based combination regimens obtain response rates ranging from 40 to 70% in first-line therapy of advanced urothelial carcinoma. In the majority of cases, however, the duration of these responses is limited, and when progression occurs, the outcome is generally poor. Therefore, novel therapeutic strategies are urgently needed. The purpose of the current research is to investigate the anticancer effects and the mode of action of the marine triterpene glycoside frondoside A in p53-wild type and p53-deficient human urothelial carcinoma cells. METHODS: Activity of frondoside A was examined in the human urothelial carcinoma cell lines RT112, RT4, HT-1197, TCC-SUP, T-24, and 486p. Effects of frondoside A on cell viability, either alone or in combination with standard cytotoxic agents were investigated, and synergistic effects were analyzed. Pro-apoptotic activity was assessed by Western blotting and FACS, alone and in combination with a caspases-inhibitor. The impact of functional p53 was investigated by siRNA gene silencing and the p53 inhibitor pifithrin-α. Effects on autophagy were studied using LC3B-I/II and SQSTM/p62 as markers. The unpaired Student's t-test was used for comparison of the data sets. RESULTS: Frondoside A shows high cytotoxicity in urothelial carcinoma cells with IC(50s) ranging from 0.55 to 2.33 μM while higher concentrations of cisplatin are required for comparable effects (IC(50) = 2.03 ~ 5.88 μM). Induction of apoptosis by frondoside A was associated with the regulation of several pro-apoptotic factors, like caspase-3, -8, and -9, PARP, Bax, p21, DNA fragmentation, and externalization of phosphatidylserine. Remarkably, inhibition of p53 by gene silencing or pifithrin-α pretreatment, as well as caspase inhibition, did not suppress apoptotic activity of frondoside A, while cisplatin activity, in contrast, was significantly decreased. Frondoside A inhibited pro-survival autophagy, a known mechanism of drug resistance in urothelial carcinoma and showed synergistic activity with cisplatin and gemcitabine. CONCLUSIONS: A unique combination of properties makes marine compound frondoside A a promising candidate for the treatment of human urothelial carcinomas.	bladder
ALK-negative anaplastic large cell lymphoma with urinary bladder involvement diagnosed in urine cytology: A case report and literature review.	Anaplastic large cell lymphoma is an aggressive T-cell neoplasm. It rarely involves the urinary bladder, with just twelve cases reported thus far and only one being ALK-negative. Immunophenotyping (particularly for ALK) is mandatory, both for prognostic and therapeutic reasons. Herein, we report the case of a patient with an ALK-negative anaplastic large cell lymphoma involving the bladder which was diagnosed and fully characterized by immunocytochemistry in urine cytology. The patient underwent a cystoscopy and the urine sample disclosed tumor diathesis background and aggregates of atypical cells, with evidence of multinucleation and mitotic figures. Immunocytochemistry revealed strong membrane/Golgi positivity for CD30 and negativity for ALK. The patient was submitted to transurethral resection for therapeutic purposes, which confirmed the diagnosis. To the best of our knowledge, this represents only the third case of anaplastic large cell lymphoma with bladder involvement diagnosed in urine cytology and the very first with diagnostic findings allowing for immunophenotyping of the disease in a bladder wash. The present report reinforces the role of urine cytology as a suitable method for establishing an earlier diagnosis and characterization of the disease, avoiding submitting patients to invasive procedures like transurethral resections. Diagn. Cytopathol. 2017;45:354-358. © 2016 Wiley Periodicals, Inc.	bladder
Lymph node density vs. the American Joint Committee on Cancer TNM nodal staging system in node-positive bladder cancer in patients undergoing extended or super-extended pelvic lymphadenectomy.	PURPOSE: We compared the prognostic value of the American Joint Committee on Cancer (AJCC) TNM nodal staging system with that of lymph node (LN) density in patients with LN-positive bladder cancer who received extended or super-extended pelvic lymphadenectomy. METHODS: Of the 1,018 patients, who underwent radical cystectomy and pelvic lymphadenectomy between February 2005 and August 2014, 110 patients with LN metastases with extended (n = 68) or super-extended (n = 42) pelvic lymphadenectomy were included. All patients were staged using the 2002 (sixth edition) and 2010 (seventh edition) AJCC TNM staging systems. The association of several variables with recurrence-free survival (RFS) and overall survival (OS) was evaluated. RESULTS: The median number of total LNs removed was 29 (6-118) and the median LN density was 12.5% (1.6%-100%). RFS and OS were not significantly different between the 2002 (pN1-pM1) and 2010 (pN1-N3) AJCC TNM nodal staging systems (sixth edition: P = 0.512 and P = 0.519; seventh edition: P = 0.676 and P = 0.671, respectively). The 2-year RFS and OS rates according to the LN density quartiles were 58.5% and 76.9% in Q1, 39.1% and 70.8% in Q2, 28.8% and 50.1% in Q3, and 12.7% and 20.8% in Q4 (P = 0.001 and P = 0.001, respectively). Multivariate analysis adjusted for the 2010 AJCC TNM staging system showed that LN density was associated with a decreased OS (HR = 1.024; 95% CI: 1.010-1.039; P = 0.001). The nodal staging system (2002 or 2010) was not associated with the RFS and OS. CONCLUSIONS: LN density shows a better prognostic value than the AJCC TNM nodal staging system in patients with LN-positive bladder cancer receiving extended or super-extended pelvic lymphadenectomy.	bladder
An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation.	PURPOSE: Chk1 inhibition increases cell sensitivity to both chemotherapy and radiotherapy in several tumour types and is, therefore, a promising anti-cancer approach. Although several Chk1 inhibitors have been developed, their clinical progress has been hampered by low bioavailability and off-target toxicities. MATERIALS AND METHODS: We characterized the radiosensitizing activity of CCT244747, the first orally bioavailable Chk1 inhibitor. We used a panel of bladder and head and neck cancer cell lines and monitored the effect of combining CCT244747 with radiation both in in vitro and in vivo models. RESULTS: CCT244747 sensitized cancer cell lines to radiation in vitro and resulted in a growth delay in cancer xenograft models associated with a survival benefit. Radiosensitization was elicited by abrogation of the radiation-induced G2 arrest and premature entry into mitosis. CONCLUSIONS: CCT244747 is a potent and specific Chk1 inhibitor that can be administered orally. It radiosensitizes tumour cell lines and represents a new therapy for clinical application in combination with radiotherapy.	bladder
Cell-Free DNA Integrity Analysis in Urine Samples.	Although the presence of circulating cell-free DNA in plasma or serum has been widely shown to be a suitable source of biomarkers for many types of cancer, few studies have focused on the potential use of urine cell-free (UCF) DNA. Starting from the hypotheses that normal apoptotic cells produce highly fragmented DNA and that cancer cells release longer DNA, the potential role of UCF DNA integrity was evaluated as an early diagnostic marker capable of distinguishing between patients with prostate or bladder cancer and healthy individuals. A UCF DNA integrity analysis is proposed on the basis of four quantitative real-time PCRs of four sequences longer than 250 bp: c-MYC, BCAS1, HER2, and AR. Sequences that frequently have an increased DNA copy number in bladder and prostate cancers were chosen for the analysis, but the method is flexible, and these genes could be substituted with other genes of interest. The potential utility of UCF DNA as a source of biomarkers has already been demonstrated for urologic malignancies, thus paving the way for further studies on UCF DNA characterization. The UCF DNA integrity test has the advantage of being non-invasive, rapid, and easy to perform, with only a few milliliters of urine needed to carry out the analysis.	bladder
The immune infiltrate in prostate, bladder and testicular tumors: An old friend for new challenges.	In genito-urinary tumors immunotherapy has been administered for a long time: Calmette-Guèrin Bacillus as adjuvant treatment in high risk patients with non muscle invasive urothelial bladder cancer and interleukin-2 and interferon-α in metastatic kidney cancer. The vaccine Sipuleucel-T has been approved by United States Food and Drug Administration for the treatment of castration resistant prostate cancer patients with asymptomatic or minimally symptomatic disease, given the 22% reduction of mortality risk in this group. Recently immunotherapeutic agents targeting inhibitory immune checkpoint molecules lead to improved outcomes and lasting anti-tumor effects in a variety of hematological and solid malignancies, including urogenital tumors. The benefit from these treatments has been observed only in a proportion of subjects, raising a need in optimizing patients' selection for immune checkpoint blockade. The composition and activity of a pre-existing immune infiltrate may aid in identifying ideal candidates to immunotherapy, with possible implications for the clinical management of neoplastic diseases from earlier to later stages.	bladder
Nomogram for predicting survival of postcystectomy recurrent urothelial carcinoma of the bladder.	PURPOSE: We aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). MATERIALS AND METHODS: Among 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. RESULTS: Of the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8-8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72-0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. CONCLUSIONS: We identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.	bladder
Urine cytology findings of primary paraganglioma of the urinary bladder: Case report.	Paraganglioma (PG) of the urinary bladder was detected in a 64-year-old male who was admitted to the hospital with gross hematuria. In voided urine, atypical cells were scattered as nests and single cells on low-power view. On higher-power view, tumor nests were composed of epithelioid cells with fine chromatin and moderate cytoplasm admixed with occasional spindle sustentacular cells. Single cells were discohesive and large with moderate cytoplasm and inconspicuous nucleoli. Subsequent cystoscopy revealed a solid oval mass. Histologically, tumor from the resected bladder showed infiltrating nested tumor cells with abundant cytoplasm. Immunohistochemically, the tumor cells were positive for synaptophysin, chromogranin, and CD56. The patient underwent partial cystectomy and was discharged without complications. Diagn. Cytopathol. 2017;45:350-353. © 2016 Wiley Periodicals, Inc.	bladder